Comparison of Native Escherichia coli L-Asparaginase versus Pegylated Asparaginase, in Combination with Ifosfamide, Methotrexate, Etoposide, and Prednisolone, in Extranodal NK/T-Cell Lymphoma, Nasal Type

Cancer Res Treat. 2018 Jul;50(3):670-680. doi: 10.4143/crt.2017.051. Epub 2017 Jul 3.

Abstract

Purpose: The aim of this study was to compare asparaginase-related toxicities in two asparaginase preparations, namely native Escherichia coli L-asparaginase (L-ASP) and pegylated asparaginase (PEG-ASP) in combination with ifosfamide, methotrexate, etoposide, and prednisolone (IMEP) in natural killer (NK)/T-cell lymphoma (NTCL).

Materials and methods: A total of 41 NTCL patients who received IMEP plus native E. coli L-ASP or PEG-ASP at Seoul National University Hospital were included in this study between January 2013 and March 2016. IMEP/ASP treatment consisted of ifosfamide, methotrexate, etoposide, plus native E. coli L-ASP (6,000 IU/m2 on days 1, 3, 5, 7, 9, and 11) or PEG-ASP (2,500 IU/m2 on day 1) every 3 weeks. ASP-related toxicities, toxicity patterns, length of hospital stay, and clinical outcomes were compared between the different treatment groups.

Results: The frequency of ASP-related toxicities was similar between the IMEP plus native E. coli L-ASP group and the PEG-ASP group apart from hypofibrinogenemia (native E. coli L-ASP vs. PEG-ASP group, 86.4% vs. 36.8%; p=0.001). Although post-treatment transaminase and albumin levels were significantly high and low, respectively, hepatotoxicity gradients before and after treatment did not differ significantly between the groups. Since PEG-ASP was given at an outpatient clinic in some patients, length of hospital stay was significantly shorter in the IMEP plus PEG-ASP group (median, 4.0 vs. 6.0 days; p=0.002). A favorable tendency of clinical outcomes was observed in NTCL patients treated with IMEP plus PEG-ASP (complete remission rate, 73.7% vs. 45.5%; p=0.067).

Conclusion: IMEP plus PEG-ASP showed similar ASP-related toxicities, shorter length of hospital stay, and a trend towards improved clinical outcomes compared with IMEP plus native E. coli L-ASP in NTCL.

Keywords: Length of stay; Native Escherichia coli L-asparaginase; Pegylated asparaginase; Toxicity; NK/T-cell lymphoma.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Asparaginase / administration & dosage*
  • Asparaginase / adverse effects
  • Escherichia coli / enzymology
  • Etoposide / administration & dosage
  • Etoposide / therapeutic use
  • Female
  • Humans
  • Ifosfamide / administration & dosage
  • Ifosfamide / therapeutic use
  • Length of Stay
  • Lymphoma, Extranodal NK-T-Cell / drug therapy*
  • Male
  • Methotrexate / administration & dosage
  • Methotrexate / therapeutic use
  • Middle Aged
  • Polyethylene Glycols / administration & dosage*
  • Polyethylene Glycols / adverse effects
  • Prednisolone / administration & dosage
  • Prednisolone / therapeutic use
  • Treatment Outcome

Substances

  • Polyethylene Glycols
  • Etoposide
  • pegaspargase
  • Prednisolone
  • Asparaginase
  • Ifosfamide
  • Methotrexate